Episodic memory, amnesia, and the hippocampal–anterior thalamic axis

TLDR

Anterograde amnesia arises from damage to an extended hippocampal system—hippocampus, fornix, mammillary bodies, and anterior thalamic nuclei—whose hippocampal efferents via the fornix are critical, while item recognition depends on a separate perirhinal–medial dorsal thalamic pathway. The hippocampal–anterior thalamic axis, through hippocampal efferents via the fornix and reciprocal diencephalic projections back to temporal cortex and hippocampus, is required for encoding and recalling episodic memory. Reanalysis of clinical and experimental data shows that most amnesic patients have lesions in both the hippocampal–anterior thalamic axis and the perirhinal–medial dorsal thalamic system, producing severe deficits in recall and recognition.

Abstract

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an "extended hippocampal system" comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampal-anterior thalamic axis is the presence of projections back from the diencephalon to the temporal cortex and hippocampus that also support episodic memory. In contrast, this hippocampal system is not required for tests of item recognition that primarily tax familiarity judgements. Familiarity judgements reflect an independent process that depends on a distinct system involving the perirhinal cortex of the temporal lobe and the medial dorsal nucleus of the thalamus. In the large majority of amnesic cases both the hippocampal-anterior thalamic and the perirhinal-medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition.